BHATIA PROGRAM
McMaster University
PUBLICATIONS
2022
The generation of human hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) represents a major goal in regenerative medicine and is believed would follow principles of early development. HSCs arise from a type of endothelial cell called a “hemogenic endothelium” (HE), and human HSCs are experimentally detected by transplantation into SCID or other immune-deficient mouse recipients, termed SCID-Repopulating Cells (SRC). Recently, SRCs were detected by forced expression of seven transcription factors (TF) (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, and SPI1) in hPSC-derived HE, suggesting these factors are deficient in hPSC differentiation to HEs required to generate HSCs. Here we derived PECAM-1-, Flk-1-, and VE-cadherin-positive endothelial cells that also lack CD45 expression (PFVCD45−) which are solely responsible for hematopoietic output from iPSC lines reprogrammed from AML patients. Using HEs derived from AML patient iPSCs devoid of somatic leukemic aberrations, we sought to generate putative SRCs by the forced expression of 7TFs to model autologous HSC transplantation. The expression of 7TFs in hPSC-derived HE cells from an enhanced hematopoietic progenitor capacity was present in vitro, but failed to acquire SRC activity in vivo. Our findings emphasize the benefits of forced TF expression, along with the continued challenges in developing HSCs for autologous-based therapies from hPSC sources.
Nature Communications, 2014
SOMATIC TRANSCRIPTOME PRIMING GATES LINEAGE-SPECIFIC DIFFERENTIATION POTENTIAL OF HUMAN-INDUCED PLURIPOTENT STEM CELL STATES
Jong-Hee Lee, Jung Bok Lee, Zoya Shapovalova, Aline Fiebig-Comyn, Ryan R. Mitchell, Sarah Laronde, Eva Szabo, Yannick D. Benoit & Mickie Bhatia
Cell Stem Cell, 2013
REGIONAL LOCALIZATION WITHIN THE BONE MARROW INFLUENCES THE FUNCTIONAL CAPACITY OF HUMAN HSCS
Guezguez B, Campbell CJ, Boyd AL, Karanu F, Casado FL, Di Cresce C, Collins TJ, Shapovalova Z, Xenocostas A, and Bhatia M
Cell, 2012
IDENTIFICATION OF DRUGS INCLUDING A DOPAMINE RECEPTOR ANTAGONIST THAT SELECTIVELY TARGET CANCER STEM CELLS
Sachlos E, Risueno R, Laronde S, Shapovalova Z, Lee JH, Russell J, Malig M, McNicol JD, Fiebig-Comyn A, Graham M, Levadoux-Martin M, Lee JB, Giacomelli AO, Hassell JA, Fischer- Russell D, Trus MR, Foley R, Leber B, Xenocostas A, Browne ED, Collins T, and Bhatia M
Nature Cell Biology, 2017
ACUTE MYELOID LEUKEMIA DISRUPTS ENDOGENOUS MYELO-ERYTHROPOIESIS BY COMPROMISING THE ADIPOCYTE BONE MARROW NICHE
Boyd AL, Reid JC, Salci KR, Aslostovar L, Benoit YD, Shapovalova Z, Nakanishi M, Porras DP, Almakadi M, Campbell CJV, Jackson MF, Ross CA, Foley R, Leber B, Allan DS, Sabloff M, Xenocostas A, Collins TJ, and Bhatia M
Cancer Cell 2016
GSK3 DEFICIENCIES IN HEMATOPOIETIC STEM CELLS INITIATE PRE-NEOPLASTIC STATE THAT IS PREDICTIVE OF CLINICAL OUTCOMES OF HUMAN ACUTE LEUKEMIA
Guezguez B, Almakadi M, D Benoit YD, Shapovalova Z, Rahmig S, Fiebig-Comyn A, Casado FL, Tanasijevic B, Bresolin S, Masetti R, Doble BW, Bhatia M
Cell Reports, 2015
SINGLE TRANSCRIPTION FACTOR CONVERSION OF HUMAN BLOOD FATE TO NPCS WITH CNS AND PNS DEVELOPMENTAL CAPACITY
Lee JH, Mitchell RR, McNicol JD, Shapovalova Z, Laronde S, Tanasijevic B, Milsom C, Casado F, Fiebig-Comyn A, Collins TJ, Singh KK, and Bhatia M
Cell, 2019
HUMAN PLURIPOTENCY IS INITIATED AND PRESERVED BY A UNIQUE SUBSET OF FOUNDER CELLS
Mio Nakanishi, Ryan R. Mitchell, Yannick D. Benoit, Luca Orlando, Jennifer C. Reid, Kenichi Shimada, Kathryn C. Davidson, Zoya Shapovalova, Tony J. Collins, Andras Nagy, Mickie Bhatia
Cancer Cell, 2018
Allison Boyd*, Lili Aslostovar*, Jennifer Reid, Wendy Ye, Borko Tanasijevic, Deanna Porras, Zoya Shapovalova, Mohammed Almakadi, Ronan Foley, Brian Leber, Anargyros Xenocostas, Mickie Bhatia
*indicates co-lead authors
IDENTIFICATION OF CHEMOTHERAPY-INDUCED LEUKEMIC REGENERATING CELLS REVEALS A TRANSIENT VULNERABILITY OF HUMAN AML RECURRENCE
Cell Stem Cell, 2011
CELL FATE POTENTIAL OF HUMAN PLURIPOTENT STEM CELLS IS ENCODED BY HISTONE MODIFICATIONS
Seok-Ho Hong, Shravanti Rampalli, Jung Bok Lee, Jamie McNicol, Tony Collins, Jonathan S Draper, Mickie Bhatia
Nature, 2010
DIRECT CONVERSION OF HUMAN FIBROBLASTS TO MULTILINEAGE BLOOD PROGENITORS
Eva Szabo, Shravanti Rampalli, Ruth M Risueño, Angelique Schnerch, Ryan Mitchell, Aline Fiebig-Comyn, Marilyne Levadoux-Martin, Mickie Bhatia
Nature Biotechnology, 2009
CHARACTERIZATION OF HUMAN EMBRYONIC STEM CELLS WITH FEATURES OF NEOPLASTIC PROGRESSION
Tamra E Werbowetski-Ogilvie, Marc Bossé, Morag Stewart, Angelique Schnerch, Veronica Ramos-Mejia, Anne Rouleau, Tracy Wynder, Mary-Jo Smith, Steve Dingwall, Tim Carter, Christopher Williams, Charles Harris, Joanna Dolling, Christopher Wynder, Doug Boreham, Mickie Bhatia
Stem Cells, 2008
OP9 STROMA AUGMENTS SURVIVAL OF HEMATOPOIETIC PRECURSORS AND PROGENITORS DURING HEMATOPOIETIC DIFFERENTIATION FROM HUMAN EMBRYONIC STEM CELLS
Junfeng Ji, Kausalia Vijayaragavan, Marc Bosse, Pablo Menendez, Katja Weisel, Mickie Bhatia
Nature, 2007
IGF AND FGF COOPERATIVELY ESTABLISH THE REGULATORY STEM CELL NICHE OF PLURIPOTENT HUMAN CELLS IN VITRO
Sean C Bendall, Morag H Stewart, Pablo Menendez, Dustin George, Kausalia Vijayaragavan, Tamra Werbowetski-Ogilvie, Veronica Ramos-Mejia, Anne Rouleau, Jiabi Yang, Marc Bossé, Gilles Lajoie, Mickie Bhatia
Nature Medicine, 2006
GLYCOGEN SYNTHASE KINASE-3 IS AN IN VIVO REGULATOR OF HEMATOPOIETIC STEM CELL REPOPULATION
Jennifer J Trowbridge, Anargyros Xenocostas, Randall T Moon, Mickie Bhatia
SELECTED PUBLICATIONS
COVER ART
Aslostovar L, Boyd AL, Benoit YD, Lu JD, Rodriguez JLG, Nakanishi M, Porras DP, Reid JC, Mitchell RR, Leber B, Xenocostas A, Foley R, and Bhatia M